1. Field of the Invention
The present invention relates to 4-hydroxytetrahydropyran-2-one derivatives, which are useful as cholesterol reducing agents as well as lipid reducing agents, more particularly which serve as inhibitors of hydroxymethylglutaryl Co-enzyme A reductase (hereinafter referred to as HMG-CoA reductase) and also has a capability of inhibiting the biosynthesis of peroxidized lipids, which is effective for curing arteriosclerosis.
The present invention also relates to intermediates for synthesizing the above 4-hydroxytetrahydropyran-2-one derivatives.
2. Discussion of Background
It is conventionally known that high-level blood cholesterol and blood lipid are significant factors relating to the development of arteriosclerosis. Therefore it is an effective treatment for arteriosclerosis to reduce the level of blood cholesterol by hindering the biosynthesis of cholesterol. Japanese Laid-Open Patent Application 50-155690 discloses ML-236B as an inhibitor which hinders the biosynthesis of cholesterol by the competitive inhibition of the effect of HMG-CoA reductase, which serves as a rate-determining enzyme for the formation of cholesterol, thereby reducing the level of the blood cholesterol in individual vital bodies.
ML-236B is a compound having a 6-substituted 4-hydroxytetrahydropyran-2-one skeleton. Following the proposal of the ML-236B, various compounds with a 4-hydroxytetrahydropyran-2-one skeleton, having a lipid-reducing effect, have been proposed, for instance, as in T. J. Lee, Trends in Pharmacol. Scie., 8(1), 4420 (1987), and Drugs of the Future 12, (5), (1987).
Furthermore, it is considered that the inhibition of the formation of peroxidized lipids will also be effective for curing arteriosclerosis, and that vitamin E and probucol has such an inhibition function.
However, none of them are sufficiently satisfactory for substantial reduction of the blood cholesterol level and the blood lipid level.